In an effort to elucidate the cell surface molecules involved both in the adhesion of cells to their substratum and in the interaction of cytoskeletal elements with the surface membrane, a series of antisera have been produced which react with cell surfaces. Several of these antisera induce reversible cell rounding and detachment from the substratum, including a monoclonal antibody which rounds and detaches chicken embryo myoblasts. An assay based upon the ability of solubilized antigen to block the effect of the antibodies permits detection of adhesion-related molecules. The successful use of the monoclonal antibody to affinity purify the antigen has stimulated progress on the structural and biochemical properties of these integral membrane glycoproteins, as well as studies designed to understand membrane-cytoskeletal and membrane-matrix interactions.